Recent epidemiological studies have suggested that GST genetic polymorphisms may affect an individual's breast cancer risk. The alleged GST effects are biologically plausible because the GST gene products catalyze the conjugation with glutathione of potentially cyto- and genotoxic reactive chemical intermediates to yield inactive products, thereby, providing a protective mechanism against cancer development. Epidemiological studies linking GST polymorphism and breast cancer risk thus far produced inconclusive results. Considering that the suggested high risk GST genotypes commonly occur in the general population, the calculated population attributable risk can be high. Against this background, a case-control study of GST genetic polymorphisms, environmental factors and breast cancer risk is proposed in Connecticut, one of the areas with the highest incidence rates of breast cancer in the United States. The primary aim of the proposed case-control study is to examine the association between genetic variability in three major GSTs, namely, GSTM1, GSTT1, and GSTP1 and the susceptibility to breast cancer. The study will (1) determine if lack of or with reduced expression of these GSTs are associated with an increased risk of breast cancer; (2) determine if the risk of breast cancer increases as the number of putative high-risk GST genotypes increases; and (3) determine if these GSTs modify the association between environmental factors and the risk of breast cancer. The blood samples used for the proposed study will come from an on- going breast cancer case-control study in Connecticut, which has recruited 349 incident breast cancer cases and 363 noncancer controls. Information on environmental exposures and other potential confounding factors has already been collected from the cases and controls by the parent study. The results from the proposed study will strengthen the parent study in searching for the risk factors that might explain the high breast cancer rate in Connecticut. Use of existing blood samples and environmental exposure data collected by the parent breast cancer study provide cost efficiency to the study. The study laboratory led by Dr. Ali-Osman, a world leader in the field of glutathione S- transferase and cancer, also represents a unique strength of the proposal.